Purpose

The aim of this study was to identify and characterize immune checkpoint inhibitors (ICIs)-associated pituitary adverse events (AEs).

Methods

This is a retrospective disproportionality study based on VigiBase, the World Health Organization (WHO) global database of individual case safety reports (ICSRs), with a study period from January 1, 2011 to March 6, 2019. Information component (IC) and reporting odds ratio (ROR) are measures of disproportionate analysis. IC was used to evaluate the association between ICIs and pituitary AEs, while ROR was used to evaluate the differences in reporting of pituitary AEs between different ICI subgroups.

Results

The following ICI-associated pituitary diseases have been increasingly reported: hypophysitis (835 reports; information component 6.74 [95% CI 6.63–6.83]), hypopituitarism (268; 6.12 [95% CI 5.92–6.27]), pituitary enlargement (28; 5.19 [95% CI 4.57–5.63]). The anti-CTLA-4 subgroup had a stronger association with hypophysitis/hypopituitarism than the anti-PD (anti-PD-1 or anti-PD-L1) subgroup (ROR 8.0 [95% CI 6.7–9.6]). Among ICI-associated hypophysitis/hypopituitarism cases, the proportion of male was higher than female (630 [63.9%] vs 356 [36.1%]). Anti-CTLA-4 subgroup and ICI combination (nivolumab plus ipilimumab) subgroup both had a significantly earlier onset time than anti-PD subgroup (67 days [IQR 48–87]; 90 [IQR 34–155]; 140 [IQR 62–218], both p < 0.05). Other endocrinopathies that co-occurred with hypophysitis/hypopituitarism were adrenal insufficiency, thyroid dysfunction, diabetes mellitus and diabetes insipidus. Gastrointestinal disorder was the most common concurrent disease except for endocrinopathies.

Conclusions

ICI-associated pituitary adverse events have significantly increased, and their clinical characteristics should be kept in mind by oncologists and endocrinologists who manage patients treated by immunotherapy.

中文翻译：

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免疫检查点抑制剂相关的垂体不良事件：一项观察性，回顾性，不成比例的研究。

目的

这项研究的目的是鉴定和表征与免疫检查点抑制剂（ICIs）相关的垂体不良事件（AEs）。

方法

这是一项基于世界卫生组织（WHO）全球个案安全报告（ICSR）全球数据库VigiBase的回顾性不成比例研究，研究期间为2011年1月1日至2019年3月6日。信息部分（IC）和报告比值比（ROR）是不均衡分析的度量。IC用于评估ICI与垂体AE之间的关联，而ROR用于评估不同ICI亚组之间垂体AE的报告差异。

结果

下列与ICI相关的垂体疾病的报道越来越多：垂体炎（835份报告；信息成分6.74 [95％CI 6.63–6.83]），垂体功能低下症（268； 6.12 [95％CI 5.92–6.27]），垂体扩大（28; 5.19 [95％CI 4.57–5.63]。与抗PD（抗PD-1或抗PD-L1）亚组相比，抗CTLA-4亚组与垂体炎/垂体功能低下的关联更强（ROR 8.0 [95％CI 6.7-9.6]）。在ICI相关的垂体增生/垂体功能减退的病例中，男性的比例高于女性（630 [63.9％]比356 [36.1％]）。抗CTLA-4亚组和ICI组合（nivolumab加上ipilimumab）亚组的发病时间均明显早于抗PD亚组（67天[IQR 48-87]； 90 [IQR 34-155]； 140 [IQR 62- 218]，两者均p <0.05）。与垂体炎/垂体功能低下症同时发生的其他内分泌病是肾上腺功能不全，甲状腺功能不全，糖尿病和尿崩症。胃肠道疾病是除了内分泌病变以外最常见的并发疾病。

结论

与ICI相关的垂体不良事件显着增加，管理免疫疗法治疗患者的肿瘤学家和内分泌学家应牢记其临床特征。